A molecular electron density theory study of Diels‐Alder reaction between Danishefsky's diene and (2E)‐3‐phenyl‐2‐(trifluoromethyl) acrylonitrile

Abstract

AbstractThe Diels‐Alder reaction between Danishefsky's diene (DD 4) and (2E)‐3‐phenyl‐2‐(trifluoromethyl) acrylonitrile (EPTA 5) at 393 K in the presence of toluene has been studied using the molecular electron density theory at the M06‐2X/6‐31G(d,p) computational level. The calculated relative Gibbs free energies indicated that the studied reaction takes place in a complete regioselective and stereoselective manner in which the most nucleophilic center of DD 4 is attacked by the most electrophilic center of EPTA 5 passing through the stationary point of TS2n. It was shown that the TS2n affords the corresponding cycloadduct of CA2n as the unique product in excellent agreement with the experimental outcomes. On the other hand, a great destabilizing steric repulsion between methoxy moiety of DD 4 and the trifluoromethyl moiety of EPTA 5 along the exo stereoselective approach is responsible for the predominance of the endo approach over the exo one. The nucleophilic and electrophilic Parr functions at the reactive sites of the DD 4 and EPTA 5 have been used to explain the regioselectivity of the Diels‐Alder reaction. According to the electron localization function analysis of the intrinsic reaction coordinate profile of the energetically most preferred TS2n, a nonconcerted two‐stage one‐step molecular mechanism has been proposed. The mechanism indicated the formation of C1C6 single bond through coupling of C1 to C6 and subsequent C4C5 single bond through coupling of C4 to C5 at cycloadduct CA2n.